William Hurlbut: Building a Bridge Over Troubled Stem Cell Waters

Prior to being appointed by President George W. Bush to the President’s Council on Bioethics in 2001, William B. Hurlbut, MD was a popular consulting professor in bioethics and the neurosciences at Stanford University, well known within the insular academic community, but not a public figure.Within just a few short years of his appointment, he became one of the world’s most prominent participants in the embryonic stem cell and human cloning research debates, whose policy perspectives were solicited at the highest government levels—including by the President of the United States.This article will explore Hurlbut’s public role in the years 2001-2008, focusing primarily on his unique effort to both advance pluripotent stem cell research and adhere to (what he considers to be) the crucial moral principle that embraces the intrinsic dignity of all human life.

William Barton Hurlbut was raised in Bronxville, NY, the son of a Park Avenue physician. Buthe could also be called a child of Stanford University. His uncle was the legendary Stanford law professor, John Bingham Hurlbut.Both his parents, his two siblings and three of his children, are also Stanford graduates. So is Hurlbut’s wife, the pediatrician Erica Goldman, who also graduated from the university’s medical school.

Hurlbut had planned a career in clinical medicine. Then, a week after graduating Stanford Medical School, his first child suffered serious brain damage at birth.To ensure the most supportive home environment, Hurlbut decided to defer residency training and accepted a post doctoral fellowship to study theology, philosophy, and biomedical ethics.

Not that Hurlbut made this decision reluctantly.His undergraduate biology major and his medical school education—studying under seminal figures in the biological revolution such as Nobel laureates Arthur Kornberg and Paul Berg—had sparked a deep passion for what is now popularly known as bioethics, and he decided to make this emerging field a focus of his professional life: “I saw vast new powers coming into our hands from our advancing scientific knowledge.” Hurlbut recalls. “I knew that this would result in unprecedented possibilities for intervention in human life. I wanted to explore the broad existential questions, that is, I hoped to help us define the target before we shot the arrow.”[i]

He joined the Stanford faculty in 1990, and quickly became a popular teacher—his classes were consistently over-enrolled—in undergraduate and graduate courses exploring bioethical issues and the interplay between medicine and technology.He also became a well regarded speaker at academic symposia and an active contributor to the professional discourse.

And that was where things might have stayed, but for the bioethicist Leon Kass. When President George W. Bush appointed Kass to head the President's Council in August 2001, he asked his new chairman to propose other potential appointees for his 18 member advisory commission. Kass included Hurlbut among the names he submitted.

Why Hurlbut? Kass had been a guest lecturer in Hurlbut's class and appreciated Hurlbut's ways of doing bioethics. "I suggested Bill because he had a solid scientific and medical background, and at the same time, a deep interest in and commitment to the larger and deeper ethical and anthropological issues raised by biomedical advance," Kass told me. "His approach was deeply humanistic (and as I later learned, also non-sectarianly theological), much richer than the narrower approaches of procedural and regulatory bioethics that had dominated previous councils." Anticipating the role Hurlbut would actually play as the contentious debate unfolded, Kass believed that he could "be a much needed bridge person between 'two cultures,' a person who would in his person display the importance of both scientific truth and of ethical philosophical depth."[ii]

Kass led the Council quickly into the hot button ethical question of whether to pursue human somatic cell nuclear transfer research.Like embryonic stem cell research, the moral status, if any, of the human embryo became the sharp entry point of the debate.

Hurlbut had long been a defender ofintrinsic human dignity, even at its most nascent stages.In a speech entitled “Stem Cells, Embryos and Ethics: Is There a Way Forward?” he argued that the issue of embryonic moral worth was a matter of great import, stating, “Assessing the moral status of the embryo begins with affirming the moral standing of human life in general.The principle that human life constitutes the fundamental good serves as the cornerstone of law for our civilization. In no circumstance is the intentional destruction of the life of an innocent individual deemed morally acceptable.”[iii]

Rejecting more subjective approaches to valuing life, such as basing moral worth upon individual capacities, Hurlbut asserted that the embryo’s moral status is inextricably connected to its biological existence as a human “organism:”

For an embryonic organism, this implies an inherent potency, an engaged and effective potential with a drive in the direction of the mature form. By its very nature, an embryo is a developing being.Its wholeness is defined by both its manifest expression and its latent potential; it is the phase of human life in which the ‘whole’ (as the unified oranismal principle of growth) precedes and produces its organic parts…To be a human organism is to be a whole living member of the species Homo sapiens, with a human present and a human future evident in the intrinsic potential for the manifestation of the species-typical form.[iv]

At the same time, unlike some opponents of human cloning (and ESCR), Hurlbut was torn.He recognized the importance of studies in developmental biology, including stem cell research, and acknowledged their therapeutic potential.

As the Council debate over human SCNT played out, Hurlbut became increasingly distressed by the polarization he witnessed—a contentiousness that reflected the larger political and societal debates swirling around the Council’s deliberations. Hurlbut recalls, “I sat there thinking, ‘There must be a better way.’I recognized both sides had good intentions and goals and asked myself, ‘Why can’t we find a technological solution that bypasses the ethical conflict?’”

The Council’s first report, Human Clonign and Human Dignity, was released in July 2002.The seventeen voting members unanimously agreed that “cloning to produce children”—more popularly known as “reproductive cloning”—“ought not be attempted.”[v]But the Council fractured badly over the propriety of pursuing human SCNT for research—sometimes called therapeutic cloning—with seven members “eager to see the research proceed,” and ten members supporting “a four-year ban on cloning…applicable to all researchers regardless of whether federal funds are involved.”[vi]

Hurlbut voted with the majority, writing in his personal statement, “Anything short of affirming the inviolability of life across all of its stages from zygote to natural death leads to an instrumental view of human life.”[vii]

But Hurlbut didn’t leave it at that.He also proposed that scientists search for a common way forward through “a speculative proposal” to develop a “clonal artificat” that would yield pluripotent stem cells without having created or destroyed a human embryo.[viii] Hurlbut further hoped that a moratorium on human SCNT would “allow the cooperative dialogue that is essential to frame the moral principles that can at once defend human dignity and promote the fullest prospects for scientific progress and its applications.”[ix]

Congress never acted to explicitly legalize or prohibit human SCNT.But Hurlbut remained convinced that if an uncontentious alternative method could be developed, it would soothe the increasingly bitter conflict playing out between “science” and what he and many others saw as proper “ethics.” He came to call his idea “altered nuclear transfer,” or ANT, and embarked on a determined personal campaign to encourage a cooperative and constructive exploration of these possibilities.

In testimony given before a U.S. Senate hearing, Hurlbut described ANT as drawing on the “basic technique of SCNT,” but without creating an embryo because prior to nuclear transfer, “the adult body cell nucleus or the enulceated egg’s contents (or both)” would be preemptively altered “in such a way that no embryo is generated, but pluripotent stem cells are produced.”[x]In a nutshell, Hurlbut hoped ANT would result in a culture of pluripotent cells lacking the integrated unity of an organism, the moral equivalent of a taratoma.

The idea initially sparked scant attention in the media, even as journalists avidly covered the roaring stem cell and human cloning controversies. Then, in late November of 2004, the Boston Globe published a front page Sunday-edition story on Hurlbut and his proposal.[xi]That broke the logjam, generating increased interest in “alternative methods,” as attempts to find non embryonic sources of pluripotent stem cells came to be called.

But would the science validate Hurlbut’s speculative hope?In October 2005, the noted stem cell researcher Rudolf Jaenisch demonstrated “proof of concept” for ANT, using mouse cells and gametes, focusing on a gene called Cdx2, which is essential for early embryonic development. The resulting collection of stem cells “proved to be just as robustand versatile as stem cells procured in the more traditional fashion.”[xii](Jaenisch made it very clear that participating in the ANT proof of concept project did not diminish his enthusiastic support for continued ESCR and human SCNT research.)But was the ANT product an embryo?No, Jaenisch later testified to a senate subcommittee, because it“lacks essential attributes of the ferilized embryo.”[xiii]

With proof of the ANT concept successfully demonstrated, Hurlbut found himself caught in a vortex of controversy.On one hand, stake holders on both sides enthusiastically backed the proposal as a bridge across the science/ethical divide.Thirty-two prominent cultural conservative opponents of human cloning research, including academics Hadley Arkes, Robert P. George, and William E. May, joined Hurlbut in issuing a joint statement of support.[xiv]Prominent scientists also supported the project. Organ transplant pioneer and Nobel laureate, Joseph E. Murray (Harvard Medical School professor emeritus) compared the emergence of organ transplant medicine and its concomitant ethical questions with the stem cell controversy.He hoped that ANT and other alternative methods could “employ the creative powers of our advancing science in an approach that both opens a positive future for biomedicine and honors and sustains full social consensus.”[xv]

But other voices raised loud objections.Some religious and pro life advocates worried that rather than creating a true non organism, ANT actually formed a “disabled embryo,” the creation and destruction of which, in their view, was no more justifiable than in SCNT. Some also raised fears about the exploitation of women for their eggs since like SCNT, ANT requires an oocyte for each nuclear transfer attempt.

Meanwhile, some bioethicists and scientists attacked ANT from a different direction. Pursuing ANT would “consume time and precious resources” Douglas A. Melton and others complained in an article published in the New England Journal of Medicine, adding “another layer of complexity” to the SCNT procedure. Moreover, where Hurlbut hoped ANT would bypass the ethical objection to pluripotent stem cell research by taking the embryo out of the equation, Melton and his co-authors believed it distracted from a debate that they clearly preferred to win, not circumvent.

Amidst the tempest, Hurlbut worked tirelessly promoting the ANT project.He traveled paripatetically—making speeches, conversing with lawmakers, conferring with scientists, consulting with bioethicists, explaining his purposes to skeptical cultural conservatives—both defending ANT and promoting the need to find a “common way forward.”He spent countless hours writing professional articles,[xvi] answering emails from academics and high school students alike, and was the subject of numerous media interviews and profiles.

Hurlbut’s efforts reached an apex in 2007 when President George W. Bush held a private Oval Office discussion with him and Dr. Don Landry, of Columbia Univeristy Department of Medicine,[xvii] inviting them to stand at his side in an East Room speech announcing the signing of an executive order requiring the NIH to give priority to funding alternative approaches. In his public comments, Bush described Hurlbut and Landry as “brilliant biologists who are seeking new ways to develop stem cell lines without violating human life.”[xviii] In the less than six years from his appointment to The President’s Council, Hurlbut had become one of the stem cell debate’s most prominent participants.

The stem cell issue has become noticably less heated since the Bush years. In part, this is due to President Obama rescinding the controversial Bush ESCR funding policy.But there is no doubt that greater comity also resulted from the announced creation in November 2007 of induced pluripotent stem cells—derived from somatic cells—validating Hurlbut’s early hope that finding non embryo destructive methods would offer a common way forward to the benefit of both science and societal accord.

Today, Hurlbut’s life is less hectic. He continues to teach popular courses at Stanford, serves on several foundation boards, and remains a high profile bioethicist, much in demand internationally as a speaker and a policy adviser. He still has high hopes for his “speculative proposal.” Indeed, Hurbult, together with colleagues Marcus Grompe, Hans Scholer, and Shoukahrat Mitalipov report “encouraging progress” in ongoing primate research on ANT under a $2.5 million NIH grant.

When asked to reflect on his role in the stem cell debates, Hurlbut said, “These are just the first controversies in the era of developmental biology; we need to seek principles that will allow us to go forward with conenseus--the stakes are just too high, not to.”[xix]

Agree with Hurlbut or not about the moral value of embryonic human life and the search for alternative methods, there is no denying his significant contributions to, and influence on, one of the most visible and important bioethical controversies of our times.